BAI TIU LUN

THUC TAC DUNG KEO DAI TRONG IU TRI BNH TIM MACHNhom 2: 1) L Thi Thuy Hng 2) Nguyn Thi Thu Hng 3) Nguyn Vn Hun 4) Hoang Huy Hung 5) Vo Quc Hung 6) Pham Thu Hng 7) Huynh ng Khoa 8) Bui Thi Nh Lp 9) Nng Thi Hai Linh 10) Trn Ba Linh 11) Trn Thi Thuy Linh

Lp Dc 5, nm hoc 2011-2012

A.TNG QUAN............................................................................................................3 A.THUC TAC DUNG KEO DAI..............................................................................7 TAI LIU THAM KHAO..........................................................................................49

A.TNG QUAN 1. Tng quan v dng thuc c tc dng ko di (TDKD) Cc dng vin thuc bo ch theo quy c c in (Conventional dosage forms) ch cha mt liu lng hot cht nht nh, khi c a vo c th s c hp thu, t n nng cc i trong mu, sau b chuyn ha, gim dn nng v b o thi ra ngoi. Nhng trong vic iu tr, vn quan trng l phi duy tr c nng nh ca hot cht trong thi gian di, nn phi dng thuc nhiu ln trong ngy (3-5 ln), s rt bt tin khi bnh nhn phi thc dy lc m khuya ung thuc va thc t iu nay khng thc hin c, nht la khi iu tri tai gia inh. S ra i ca dng thuc c TDKD gii quyt c vn . Thuc TDKD l nhng ch phm c kh nng gii phng dc cht lin tc theo thi gian duy tr nng thuc trong mu trong phm vi iu tr trong mt khong thi gian di nhm nng cao hiu qu iu tr, gim bt tc dng ph ca thuc v gim s ln dng thuc cho ngi bnh Thuc TDKD c mt trong nhiu nhm thuc iu tr cc bnh khc nhau. Bi tiu lun ny ch cp n nhm thuc iu tr cc bnh v tim mch. 2. Tng quan thuc iu tri bnh tim mch Thuc tc dng trn h tim mch bao gm: Thuc iu tr suy tim Thuc iu tr ri lon nhp tim Thuc chng cn au tht ngc Thuc h lipid mu Thuc chng huyt khi Thuc iu tri tng huyt ap Thuc iu tri ha huyt ap

Trong danh sach trn, hai nhom thuc iu tri tng huyt ap va ha huyt ap c xp ring va khng thuc pham vi tim hiu cua bai tiu lun nay. Tuy vy, trong iu tri bnh tim mach co nhng nhom thuc c s dung chung la iu kho tranh khoi. Chung i khi la thuc chu tri, cung co luc la thuc phi hp cac mc quan trong khac nhau. Vi vy, vic gii thiu tng quat v cac nhom thuc iu tri bnh tim mach la cn thit, nhng gii thiu nhng nhom thuc cu th (nh thuc chen knh Calci) thi se xay ra trung lp cac nhom bnh tim mach. Do o bai tiu lun chi gii thiu tng quat khi chung co dang TDKD. 2.1. Thuc iu tr suy tim Suy tim l trng thi bnh l, trong cung lng tim khng p ng nhu cu oxy cho c th trong cc trng thi sinh hot ca ngi bnh. Cc thuc iu tr suy tim l nhng thuc lm tng cung lng tim bng cch tc ng vo cc yu t nh hng ti cung lng tim, c th l: Tng sc co bp c tim Gim tin gnh v hu gnh Gim mui, nc Cc nhm thuc iu tr suy tim gm: Glycosid tr tim Thuc lm tng AMPv Thuc c ch men chuyn Thuc chn -adrenergic 2.2. Thuc iu tr ri lon nhp tim Thuc iu tr ri lon nhp tim l nhng thuc c tc dng iu ha nhp tim khi nhp tim b ri lon (chch khi nhp tim bnh thng).

Thuc ch iu tr triu chng, ngn nga hoc ct cn ri lon nhp tim do bt k nguyn nhn no bng cch: Lm gim tnh t ng ca tim Hoc tng tnh t ng, rt ngn thi gian tr Lm gim tnh dn truyn Cc nhm thuc iu tr ri lon nhp tim gm: Thuc chn knh Na+ Thuc chn -adrenergic Thuc chn knh K+ Thuc chn knh Ca++ 2.3. Thuc chng cn au tht ngc Nguyn nhn ca cn au tht ngc l do c tim b thiu oxy t ngt v mt thng bng gia tng nhu cu oxy ca c tim v s cung cp khng oxy ca mch vnh. Thuc iu tr cn au tht ngc hot ng theo c ch: Tng cung cp oxy cho c tim Lm gim mc tiu th oxy ca c tim Lm phn b li mu c li cho vng thiu mu Lm tan huyt khi trong lng mch Bo v t bo c tim khi thiu mu Cc nhm thuc iu tr au tht ngc gm: Nitrat hu c Thuc chn -adrenergic

Thuc chn knh Ca++ Aspirin, Dipyridamol Trimetazidin 2.4. Thuc chng huyt khi Thuc chng huyt khi gm 2 loi: 2.4.1. Thuc chng ng mu (ngn chn khng cho mu ng) Thuc c ch cc yu t ng mu: heparin Thuc khng vit K: dn xut coumarin, indandion Thuc chng ngng tp tiu cu: aspirin, dipyridamol 2.4.2. Thuc tiu fibrin (lm tan cc mu ng) Streptokinase 2.5. Thuc h lipid mu Thuc h lipoprotein mu hot ng theo cc c ch: Lm gim hp thu v tng thi tr lipid qua ng tiu ha c ch tng hp lipid C ch khc Cc nhm thuc h lipid mu: Cc resin chelat ha Cc dn xut statin Cc dn xut ca acid fibric Niacin[54]

A. THUC TAC DUNG KEO DAI Cac nhom thuc co dang TDKD bao gm: Thuc nitrat hu c Thuc chn -adrenergic Thuc chen knh Calci Thuc chen knh Natri Thuc ha lipid mau (acid nicotinic, dn xut acid fibric) 3. Thuc nitrat hu c 1.1. ai cng nhom nitrat hu c C ch tac dung Receptor ca nitrat c cha nhm sufhydryl, nhm ny kh nitrat v c v nitric oxid (NO). NO kch thch Guanylat cyclase lm tng GMP vng. GMP vng xc tc phn ng to myosin-LC l cht gin c. C ch ny tng t c ch gin mch ca nitroprussid[48]. 3.1. Hoat cht co dang TDKD 3.1.1. Nitroglycerin 3.1.1.1. Ch phm quy c a. Tinh cht ly hoa - Nitroglycerin l mt cht lng khng mu, nht, to thnh t phn ng nitro ha glycerin, rt d n. - Danh phap IUPAC: propane-1,2,3-triyl trinitrate - Cng thc ha hc: C3H5(NO3 )3

- M = 227.0872 -Nhy n vi va chm va ma sat -im nng chy: 13.2C (55.76F) - im pht n: 50C n 60C (12F to 140 F) - Cu trc: [28]

b. Dc ng hoc Thuc c s dng theo ng tnh mch, ng ung, qua da, di li. Ngm di li: hp thu thuc nhiu hn v nhanh hn l ung bi v trnh c s chit khu mt t l ln lng thuc khi qua gan ln th nht, m i ngay vo i tun hon v tim. Dc ng hoc cua Nitroglycerin dang ngm di li: Nitroglycerin t c hiu lc khi ung do b thy phn d dy v b thoi ging mnh khi qua gan. Cho ngm di li, thuc c hp thu nhanh chng v hon ton, cc chuyn ha ca thuc trong huyt tng v trong hng cu khng nhiu nn cho php thuc vo c trong cc t bo c trn thnh mch v lm gin mch; thuc bt u c trong huyt tng sau 30 giy, t mc ti a sau 2 pht, thi gian bn hy huyt tng l 3 - 4 pht. Nh vy tc dng ca glyceryl trinitrat ngn, bt u sau 0,5 - 2 pht, ko di 30 pht. Dn cht Mononitrat c li im hn Dinitrat v: thi gian bn hy di hn, chu t l chit khu t hn khi qua gan ln th nht. Hm lng trong huyt tng t hiu qu ca Trinitrin l 1 ng/ml. [14] c. Chi inh - liu dung

Chi inh +Phng v iu tr cn au tht ngc. +iu tr suy tim sung huyt (phi hp vi cc thuc khc). +Nitroglycerin cn c dng trong nhi mu c tim cp, tuy vy chi inh nay vn ang c cn nhc. [14] Liu dung iu tr ct cn au tht ngc: Ngm di li mt vin nitroglycerin 0,5 mg (thng t 0,3 - 0,6 mg), c sau 5 pht li ngm 1 vin cho n ht cn au, ti a khng qu 3 ln. C th dng dng kh dung xt li, mi ln xt 0,4 mg, xt 1 - 2 ln vo di li ngm ming, khng ht. Trong ngy c th dng li nhiu ln nu cn au li ti din v ngi bnh khng b au u, h huyt p. Tom tt liu dung cua mt s ch phm thng thng [14] Tn bit dc Lenitral Natispray Nitro-Bid IV Thi gian khi u tc dng (pht) 1-3 2-4 1-2 Thi gian tc dng 10-30 pht 10-30 pht 3-5 pht

Tn thuc Ngm di li Xt di li IV

Liu thng dng 0,4-0,6 mg 0,4mg/ln xt Khi u 5mg/pht, tng mi 3-5 pht cho n khi gim au hoc khi huyt p h.

3.1.1.2. Ch phm TDKD Cac dang bao ch TDKD gm co: Dang vin (vin nen va vin nang), dang ming dan trn da va dang thuc m. Dng ming thuc dnh vo da: thng dn vo vng ngc tri, mi ming dn cha 5-10 mg nitroglycerin. Thuc ngm qua da, gii phng thuc u n trong 24 gi, c tc dng sau 30 - 60 pht, nng trong huyt tng n nh sau 24 gi, gim nhanh

sau khi ngng dn. Co cac ch phm vi ham lng 0,1 mg, 0,2 mg, 0,3 mg, 0,4 mg, 0,8 mg/gi. Dng thuc m: Thuc thm qua da, c tc dng sau 15 - 60 pht. Thng dang 2%. Vin gii phng ko di: 1 mg, 2 mg, 3 mg, 5 mg. Nang gii phng ko di: 2,5 mg, 6,5 mg, 9,0 mg. [14] Mt s bit dc cu th Dang bao ch Thuc m Thi gian khi u tc dng (pht) 30 30 30 30 30 30 1-3 Thi gian tc dng 4-8 gi 3-4 gi 4-8 gi 8-12 gi 8-12 gi 8-12 gi 30 pht7 gi Liu thng dng 1/2-2 inch/4 gi (1 inch=15mg) 0,08 mg/gi 0,2-0,4 mg/gi 0,2-0,8 mg/gi 0,2-0,6 mg/gi 0,2-0,8 mg/gi 0,2-0,3 mg/gi

Tn bit dc Nitro-Bid [26] Lenitral [17] Militran [48] Nitroderm TTS [27]

Hm lng 2% 2% 5mg, 10mg 5mg,10mg, 20mg 5mg, 10mg, 15mg 5mg, 10mg, 20 mg 2,5mg; 7,5mg

Bng dinh

Diafusor [8] Cordipatch [7]

Vin nang

Lenitral [18]

Mt s im lu y: - Dang thuc m: Nn 0,5-2 inch thuc m vo giy c chia liu km theo tuyp thuc. t mnh giy ln ngc v thoa u mt lp mng 2 inch x 2inch. - Dng tc dng ko di nh thuc m hay ming bng dnh hoc dng ung d gy dung np, nn hoch nh ch liu sao cho khong thi gian khng dng nitrat trong ngy l 10-12 gi. Mt s hinh anh

Nitroderm TTS

Thuc m Nitro-bid 2%

Dang vin nang 3.1.2. Isosorbide mononitrate v Isosorbide dinitrate 3.1.2.1. Ch phm quy c a. Tinh cht ly hoa Isosorbide dinitrate: nguyn cht dang bt kt tinh mau trng. Nhit nong chay 69-72oC. Tan rt it trong nc, tan c trong ethanol, ether, aceton N do nhit va va cham. b. Dc lc hoc - Dc ng hoc Dc lc hoc

Isosorbide mononitrate l cht chuyn ha c hot tnh ca Isosorbide dinitrate, lm dn c trn mch mu, dn n dn cc tnh mch v ng mch nhng tc ng lm gim cc tnh mch th tri hn.Tc dng iu tr ph thuc vo liu s dng. Nng thuc thp trong huyt tng c tc dng lm gin tnh mch, dn n tng cha mu ngoi vi, gim hi lu mu tnh mch v lm gim p lc cui k tm trng tht tri (tin ganh). Nng thuc cao trong huyt tng cng lm gin ng mch, do lm gim sc cn mch mu v huyt p dn n gim hu ganh. Isosorbide mononitrate cng c tc dng trc tip lm gin ng mch vnh. Bng cch lm gim th tch v p lc cui k tm trng, thuc lm gim p lc trong thnh c tim, do lm ci thin mu di ni tm mc. Do tc dng tng hp ca Isosorbide mononitrate l lm gim ti cho tim v ci thin cn bng cung/cu oxy cho tim. [44] Dc ng hoc Isosorbide dinitrate t di li co nng ti a trong mau sau 6 phut, t1/2 khoang 45 phut. Cht chuyn hoa ban u la isosorbide 2-mononitrate va isosorbide 5mononitrate vn con hoat tinh. [54] Isosorbide mononitrate c hp thu hon ton v khng b chuyn ha trong giai on u i qua gan. iu ny lm gim tnh bin thin nng thuc trong huyt tng v dn n tc dng lm sng n nh. Thi gian bn thi ca Isosorbide mononitrate l khong 5 gi. Th tch phn b ca Isosorbide mononitrate vo khong 0,6 L/kg v thanh thi ton phn vo khong xp x 115 mL/pht. S thi tr xy ra do qu trnh thi tr nit v phn ng lin hp. Cc cht chuyn ha c bi tit ch yu qua thn. Ch khong 2% liu c s dng bi tit di dng khng i qua thn. [44] c. Chi inh - liu dung Isosorbide mononitrate: - Chi inh: ngn nga s xut hin ca nhng giai on thiu mu cc b trong cn au tht ngc.

- Vin nn khng bao 10mg, 20mg. S dng 2 vin/ ngy, hai liu cch nhau 7h. Mt s bit dc nh Lisorbide, Vasotrol, Monotrat - ng ung: C th bt u iu tr vi 10 mg/ngy trong 2 ngy, sau l 10 mg 3ln/ngy trong 3 ngy trnh cc tc dng ph c bn cht thong qua ph thuc vo liu, hai liu cch nhau 7h. Sau c th tng liu ln 20 mg 2-3 ln/ngay. C th dng ti 40 mg 2-3/ln/ngy. Liu dng ti a khng nn vt qu 120 mg. [21] Isosorbide dinitrate: - ng ngm di li: vin 5 mg + Cn au tht ngc: 5-10 mg, ngm tip tc nu cn au ti pht. + Ph phi cp tnh: 5-10 mg, phi hp vi iu tr kinh in. - ng ung: vin 5 mg, 10 mg. Mt s bit dc nh Apo-ISPN, Biresort, Sorbidin, Risordan Mt s chi inh - liu dung cua bit dc Risordan dang tac dung nhanh [37] Chi inh Phng nga cn au tht ngc Suy tm tht tri hay ton phn Suy tim tr Liu ban u Risordan dang ung 2-3 ln/24 gi. Nh trn Liu duy tri iu chinh tuy trng hp cu th Nh trn Liu thng thng 10-60 mg/24 gi chia lm 2-3 ln 20-60 mg/24 gi chia lm 2-3 ln Liu dng c tng dn ln n ti a l 240 mg/24 gi

- Dch tim - truyn ( 0,1%): Bit dc Isoket 0,1%, Isobid - Dng thuc xt hng. Bit dc Iso mack spray. Xt 1-3 ln vo khoang ming, mi ln cch nhau 30s 3.1.2.2. Ch phm TDKD a. Dng thuc cha Isosorbide mononitrate [16]

Hm lng Tn bit dc ( tnh theo lng Dng bo ch Isosorbide mononitrate ) Dng thuc c mt ti Vit Nam Imdur 30mg, 60mg Vin nn phng thch ko di ISMN 40 stada retard 40mg Vin nn phng thch ko di ISMN 60 stada retard 60mg Vin nn phng thch ko di Isomornit 60 retard 60mg Vin nn phng thch ko di Isosorbide mononitrate Vin nn gii phng c kim 30mg Vellpharm sot Vin nn gii phng c kim Mohero CR 30mg sot Vasotrate OD 30mg, 60mg Vin nn phng thch ko di Isoroco 30 SR 30mg Vin nn phng thch ko di Isoroco 60 SR 60mg Vin nn phng thch ko di Mt s dng thuc khng c mt ti Vit Nam Monocinque retard 50mg Vin nang phng thch ko di Elantan Long 50mg Vin nang phng thch ko di Sorbinate SR 60 60mg Vin nn phng thch ko di Monolin SR 20mg, 60mg Vin nang phng thch ko di Imdex 60mg Vin nn phng thch ko di Mt s c im cua bit dc Imdur (TDKD) [44] Cng thc vin (Imdur) +Hoat cht: isosorbide-5-mononitrate +Ta dc: Hydroxypropylcellulose, sodium aluminum silicate, magnesium stearate, colloidal silicon dioxide, polyethylene glycol, titanium dioxide, iron oxide yellow, parrafin. Dc ng hc - Tn thng chc nng gan v thn khng nh hng n qu trnh hp thu ca thuc. - Kh nng phng thch hot cht khng ph thuc vo pH trong khong thi gian 10h. So snh vi cc vin nn thng thng, giai on hp thu v thi gian tc ng ko di hn. Sinh kh dng xp x 90% so vi vin nn phng thch tc th. S hp thu khng b nh hng ng k ca thc n. Nng thuc ti a trong huyt tng

(khong 3000mmol/L) t c khong 4h sau khi lp li liu ung duy nht 60mg/ ngy. Nng thuc trong huyt tng gim dn n khong 500 mmol/L vo thi im cui ca cc liu thuc (24h sau khi ung thuc). - Bang so sanh dc ng hoc cua liu thng thng va ch phm TDKD

n liu Thng s ISMN Imdur 60mg Cmax (ng/mL) 1242-1534 424-541 Tmax (h) 0.6-0.7 3.1-4.5 AUC (ng.h/mL) 8189-8313 5990-7452 t1/2 (h) 4.8-5.1 6.3-6.6 Cl/F (mL/mi) 120-122 151-187 (ISMN: Isosorbide mononitrat) Liu dng cch dng

a liu ISMN 60mg Imdur 120mg 557-572 1151-1180 2.9-4.2 3.1-3.2 6625-755 14241-16800 6.2-6.3 6.2-6.4 132-151 119-140

- S dng 1 ln/ngy vo bui sng. Liu c th tng ln gp i. gim thiu kh nng b nhc u, liu khi u c th gim xung mt na so vi liu iu tr quy nh trong 2-4 ngy u tin. C th dng hoc khng dng chung vi thc n. b. Dng thuc cha Isosorbide dinitrate [16] Hm lng Tn bit dc ( tnh theo lng Dng bo ch Isosorbide dinitrate ) Dng thuc c mt ti Vit Nam Iso mack retard 20mg, 40mg Vin nang phng thch ko di Risordan LP 20mg Vin nn phng thch ko di Mt s dng thuc khng c mt ti Vit Nam Cedocard retard 20mg Vin nn phng thch ko di Dilatrate SR 40mg Vin nang phng thch ko di Mt s c im cua bit dc Risordan LP 20 mg [37] Dc ng hoc

Sau khi ung mt liu duy nht Risordan LP 20 mg, nng huyt tng ca isosorbide dinitrate t ti a sau 40 pht v gi trong vng 6 gi, sau 10 gi vn cn ng k. Nng huyt tng ti a gi n nh trong khong 10 gi i vi isosorbide dinitrate v 12 gi i vi cc cht chuyn ha mononitrate. Chi inh - liu dung

Chi inh Phng nga cn au tht ngc Suy tm tht tri mau Suy tim tr

Liu dung (ng ung) 40-80 mg/24 gi chia lm 2 ln Cach nhau 12 gi 20 mg, 2-3 ln/24 gi, cach khoang 12 gi Co th tng n 40 mg, 2 ln/24 gi, khng i xng (Vi du: 8h - 18h) Dang TDKD c bit thich hp va c u tin s dung

3.1.3. Pentaerythritol tetranitrate Dng thuc ch phm quy c: 10mg, 20mg, 40mg (Duotrate, Pentylan ) Dng thuc ko di : 80mg (Peritrate ) - Ch nh : S dng trong d phng cn au tht ngc.Tr suy tim vnh sau nhi mu c tim (c bit l suy tim tri nng bn cp ) [53] - Dc ng hc: thi gian hp thu sau khi ung l 20 60 pht.Thi gian thi tr hon ton ca dng bo ch bnh thng l 5h, thi gian thi tr hon ton ca dng bo ch ko di l khong 12h. Pentaerythritol tetranitrate c chuyn ha qua gan ln u, v c thi tr gn nh hon ton qua nc tiu. [30] 3.2. Thuc chng au tht ngc cu truc khac nitrat Trimetazidine Tinh cht ly hoa: Bt kt tinh mau trng, hut m nhe. D tan trong nc, tan va trong ethanol.

Ch phm qui c Bit dc VASTAREL

Ch phm TDKD VASTAREL MR

Dc ng hc

Tc dng

-Thuc c hp thu nhanh v t nng ti a trong mu trc 2 gi sau khi ung thuc. -Nng ti a trong huyt tng t c sau khi dng liu duy nht 20 mg trimtazidine vo khong 55 ng/ml. - Tnh trng cn bng, t c t Trimetazidine MR t nng nh 24 n 36 gi sau khi dng cc liu cao hn trong huyt tng vi bin lp li, rt n nh trong qu trnh dao ng 24 gi trong huyt iu tr. tng t hn so vi dng phng - Th tch phn phi l 4,8 l/kg, thch nhanh. [51] gn kt vi protine huyt tng thp, trong khong 16%. -Ch yu c o thi qua nc tiu di dng khng b bin i. -Thi gian bn hy o thi trung bnh l 6 gi [41] -Ci thin tnh trng thiu mu cc b bng cch ngn chn qu trnh Ci thin tnh trng thiu mu cc oxy ha a xt bo ni bo, dn n b bng cch ngn chn qu trnh tng nng lng pht sinh t oxy oxy ha a xt bo ni bo, dn n ha ng tng nng lng pht sinh t oxy -Ngoi ra cn ci thin cc thng s ha ng. [47] lipid huyt tng. [47] iu tr d phng cn au tht ngc.[41] 40-60mg/24h, tng ng 2-3 vin/ngy, chia lm 2-3 ln trong cc ba n.[41] iu tr d phng cn au tht ngc, c bit thch hp cho bnh nhn au tht ngc n nh.[47] Ngy 2 ln [42]

Ch nh

Liu dng

Dng bo ch

Thuc ung git Vin nn bao phim Vin nn [42]

Vin bao phim dng phng thch chm [42]

Hnh nh

4. Thuc chen -adrenergic 4.1. ai cng thuc chen -adrenergic (-Blocker) 4.1.1. C ch tac dung - Cc thuc chn -adrenergic l nhng cht i khng theo c ch cnh tranh i vi cc Catecholamin. S c ch c hiu ny thng qua cc th th -adrenergic ca h thn kinh giao cm. - Thuc c ch hot ng ca cc th th -adrenergic nm trong mng t bo, v d t bo si c tim hay si c lp trung mc tiu ng mch. Cc th th ny n nhn noradrenalin t u mt cc dy thn kinh giao cm tit ra to nn hiu qu cng giao cm. Cac -Blocker co cu truc tng t vi noradrenalin, chim ch receptor ma khng gy ra kich thich. l s c ch theo c ch cnh tranh. [39] 4.1.2. Cac phn nhom Da vao vi tri va c ch, thuc -Blocker c chia lam 2 nhom: - Khng chon loc (c ch ca 1 va 2): propranolol, labetalol, sotalol, timolol, pindolol, alprenolol, oxprenolol

- Chon loc trn 1: atenolol, acebutolol, metoprolol, practolol, betaxolol, esmolol Cac thuc noi chung ging nhau v tac dung, c ch tac dung, chi khac v cng tac dung va mt s c im ring. [55] Mt s c im tac dung cua cac thuc in hinh c tom tt nh sau [55] Chon loc trn 1 Acebutolol (Sectral) + Atenolol (Ternomin) + Betaxolol + Esmolol + Metoprolol (Lopressor) + Carvedilol * Labetalol * Pindolol (Visken) Propranolol (Avlocardyl, Inderal) Sotalol (Sotalex) Timolol (Timaco, Blocadren) (+): Co (-): Khng Tn thuc - bit dc 4.2. Hoat cht co dang TDKD 4.2.1. Metoprolol 4.2.1.1. Ch phm quy c a. Tinh cht ly hoa - Danh phap metoprolol: (2-hydroxy-3-(4-(2-methoxyethyl) phenoxy) propyl) (propan-2-yl)amine - Cng thc phn t: C15H25NO3 - M = 267,3639 - Co 2 dn xut ph bin la (Lopressor). [20] metoprolol succinat (Egilok) va metoprolol tatrat Cng giao n inh mang cam ni tai + + + + + + (*): c ch ca 1

b. Dc ng hoc - Hp thu: thuc hp thu tt qua ng ung khong 95%. -Phn b: Metoprolol it lin kt vi protein huyt tng, khong 11%. Metoprolol tan trong lipid, chuyn ho qua gan ln u nhiu nn sinh kh dng thp, khoang 40%. Thuc qua c hng ro mu no, c th gy tc dng khng mong mun trn thn kinh trung ng. - Chuyn ho: qua gan. - Thi tr: thi gian bn thi ngn, 3-5 gi. Thi tr nhiu qua mt.

c. Chi inh - liu dung Chi inh - Tng huyt p. - au tht ngc, lon nhp tim. - iu tr duy tr sau nhi mu c tim. - Hi hp do bnh tim chc nng, cng gip. - D phng au na u. Liu dung Vi ch phm vin nen Metoprolol succinat (Egilok), co cac ham lng: 25, 50, 100 mg. - Tng huyt p 50mg ngy 1 ln hay chia 2 ln, c th tng dn ln 100-200mg/ngy, ti a 400mg/ngy. - au tht ngc, lon nhp tim 100-200mg/ngy chia 2 ln, c th tng ln 400mg/ngy. - iu tr duy tr sau nhi mu c tim 200mg/ngy, chia 2 ln. - Hi hp do bnh tim chc nng, cng gip 100mg/ngy chia 2 ln, khi cn tng ln 400mg/ngy.

- Nhp tim nhanh trn tht: Liu khi u: ung 100 mg/ln hoc chia 2 liu. Liu duy tr: 100 n 450 mg/ngy. [19] 4.2.1.2. Ch phm TDKD a. Betaloc Zok - Ham lng 1 vin tc dng ko di bao gm: 23,75 mg, 47,5 mg, 95 mg hoc 190 mg metoprolol succinate tng ng vi 25 mg, 50 mg, 100 mg hoc 200 mg metoprolol tartrate - Betaloc Zok bo ch bng cch ng gi gm nhng ht ring bit v mi ht cha 1 lng metoprolol succinate. Mi ht c ph mt mng polymer, kim sot tc giai phng ca thuc. Vin thuc tan r nhanh chng khi tip xc vi dich tiu hoa. Cc ht ny c phn tn trn mt b mt ln trong ng tiu ha. Thuc gii phng lin tc trong 20 gi khng b nh hng ca pH mi trng. [4] Chi inh - liu dung: - Cao huyt p: 50-100 mg mi ngy mt ln. nhng bnh nhn khng p ng vi 100 mg, c th kt hp vi cc thuc h huyt p, tt nht l thuc li tiu v thuc i khng calci ca cc loi dihydropyridin, hoc tng liu. - au tht ngc: 100-200 mg/ln/ngay. Nu cn c th kt hp vi nitrat hoc tng liu/ln. [4] b. Cac bit dc khac: Toprol XL 4.2.2. Propranolol 4.2.2.1. Ch phm quy c a. Tinh cht ly hoa - Bt kt tinh mau trng, khng mui, vi ng. Bn vi nhit nhng bi bin mau bi anh sang.

- Tan trong nc, ethanol, kho tan trong dung mi hu c khac. b. Dc ng hoc - Hp thu: Propranolol c hp thu gn hon ton ng tiu ha. Sau khi ung 30 pht xut hin trong huyt tng, v sau 60 - 90 pht t nng ti a. - Phn b: Propranolol c phn b rng ri vo cc m trong c th, k c phi, gan, thn, tim. Thuc d dng qua hng ro mu - no, vo nhau thai v phn b c trong sa m. Trn 90% propranolol lin kt vi protein huyt tng. - Chuyn hoa: c chuyn ha gn hon ton gan; c t nht 8 cht chuyn ha c tm thy trong nc tiu. - Thai tr: Ch 1 - 4% liu dng c thi qua phn di dng khng chuyn ha v dng chuyn ha. ngi bnh suy thn nng, c s tng o thi b tr qua phn. [35] c. Chi inh - liu dung Dng ch phm quy c: Vin nn: 10, 20, 40, 60, 80, 90 mg; dung dch: 20 mg/5 ml; 40 mg/5 ml; 80 mg/5 ml - Tng huyt p: Liu dng phi da trn p ng ca mi c th. Khi u: 20 - 40 mg/ln, 2 ln/ngy, dng mt mnh hoc phi hp vi thuc li tiu. Tng dn liu cch nhau t 3 - 7 ngy, cho n khi huyt p n nh mc yu cu. Liu thng thng c hiu qu: 160 - 480 mg hng ngy. Mt s trng hp phi yu cu ti 640 mg/ngy. Thi gian t c p ng h p t vi ngy ti vi tun. Liu duy tr l 120 - 240 mg/ngy. Khi cn phi hp vi thuc li tiu thiazid, u tin phi hiu chnh liu ring tng thuc. - au tht ngc: Liu dng mi ngy c th 80 - 320 mg/ngy ty theo c th, chia lm 2 hoc 3, 4 ln trong ngy, vi liu ny c th tng kh nng hot ng th lc, gim biu hin thiu mu cc b c tim trn in tm . Nu cho ngng iu tr, phi gim liu t t trong vi tun. Nn phi hp propranolol vi nitroglycerin. - Lon nhp: 10 - 30 mg/ln, 3 - 4 ln/ngy, ung trc khi n v trc khi ng.

- Nhi mu c tim: Liu mi ngy 180 - 240 mg, chia lm nhiu ln. Cha r hiu qu v an ton ca liu cao hn 240 mg phng trnh t vong do tim. Tuy nhin cho liu cao hn c th l cn thit iu tr c hiu qu khi c bnh km theo nh au tht ngc hoc tng huyt p. - phng nhi mu ti pht v t t do tim, sau cn nhi mu c tim cp, cho ung 80 mg/ln, 2 ln/ngy, i khi cn n 3 ln ngy. [35] 4.2.2.2. Ch phm TDKD Half-Inderal LA (nh sn xut: Astra Zeneca) - Dang bao ch: Vin nang, ham lng 80 mg - Cao huyt p: Liu ban du l 80 mg, mi ngy mt ln, c th s dng mt mnh hoc thm vo thuc li tiu. Liu dng c th c tng ln 120 mg mi ngy mt ln hoc cao hn cho n khi kim sot huyt p mc ti u. Liu duy tr thng thng l 120 n 160 mg mt ln hng ngy. - au tht ngc: Liu ban u 80 mg mi ngy mt ln, liu lng phi c dn dn tng ln ba n by ngy cho n khi n nh. - au na u: Liu ung ban u l 80 mg mi ngy mt ln. Phm vi liu hiu qu thng thng l t 160 n 240 mg mi ngy mt ln. [15]

5. Thuc chen knh Calci 5.1. ai cng thuc chen knh calci (Calcium channel blocker - CCB) 5.1.1. C ch tac dung Hu ht c trn u ph thuc vo dng Ca2+ xuyn mng t bao thc hin chc nng bnh thng nh co c, do tt c CCB lm gin c trn, nht l c trn mch mu. Hot ng ca c tim ph thuc dong Ca2+. c ch dng Ca2+ pha 2 in th hot ng lm gim co c tim v gim dn truyn tim. [48]

Hnh: Vai tr sinh l ca calci trn tim mch [52] VOC: knh hot ng theo in p SR: li bo tng Vy tc dng ca CCB gp phn iu tri au tht ngc gm c: - Gin mch vnh nn tng cung cp oxi cho c tim. - Gin mch ngoi vi nn gy gim hu gnh v gim co tht c tim gp phn gim tiu th oxi ca c tim. C ch ny u th hn c ch tng cung cp oxi cho c tim.[48] 5.1.2. Cac phn nhom

Bang tom tt mt s c im va phn loai cac thuc CCB [52] Nhm ho hc Tc dng c hiu Th h 1 Th h 2 Felodipin Nicardipin Nimodipin Amlodipin Isradipin Th h 3 Tc dng ph Nhn xt chung

Tc dng ph: h HA nhanh, ng Dihydropyridin Nifedipin Lacidipin hi hp, ph mt mch>tim c chn, bLock A-V. Chng ch ng Benzothiazepin Diltiazem Clentiazem nh: suy tim, mch=tim nhp chm Phenyl alkyl ng Gallopamid xoang, block AVerapamil amin mch50 4-6 10-50 6-12 220Ib (>100kg) - Ch phm: Procanbid vin Procanbid 500 : Mu trng, bao phim, vin nn hnh elip, c in Procanbid 500 1 bn. Liu lng 1000mg/12gi 1500mg/12gi 2000mg /12gi 2500mg/12gi

Procanbid 1000: Mu xm, bao phim, vin nn hnh elip, c in Procanbid 1000 2 mt.

b. Pronestyl-SR Pronestyl-SR vin nn ung c cha 500 mg procainamide hydrochloride, mu vng, hnh elip, bao phim, l thuc phng thch ko di. [33] - Cng thc bo ch: Procainamide hydrochloride

Microrystalline cellulose Silicon dioxide Acid stearic Cht mu (D&C Yellow 10, FD&C Green 2 ) Thnh phn khc - Dc ng hc: Sau khi dc cht c hp thu th nng dc cht trong mu c duy tr trong sut khong thi gian dng thuc l 12gi. - Liu dng: Liu c th ti 50 mg/kg th trng/24 gi. Trng lng 88-100Ib (40-50kg) 132-154Ib (60-70kg) 176-198Ib (80-90kg) >220Ib (>100kg) - Ch phm: Vin nn Pronestyl-SR Liu lng 500mg/6gi 750mg/6gi 1g/6gi 1,25g/6gi

c. Procan SR Procan SR l vin nn, dng phng thch ko di. [34]

- Cng thc chung bo ch vin nn Procan SR:

Hydrochloride procainamid Calcium silicate Sp carnauba NF Diethyl phthalate Dimethyl polysiloxane Ethyl cellulose Hydroxypropyl methylcellulose USP

Magnesi stearat Vanillin Titanium dioxide Polysorbate 80 Polyethylene glycol Nhm

- Cc thnh phn khac ca vin co ham lng khac nhau: Procan SR 500MG: D&C Red 30.. Procan SR 750MG: D&C Yellow 10, FD&C Yellow 6. Procan SR 1000MG: FD&C Red 40. - H ct ca vin tc dng ko di Procan c h ct khng bi hp thu, c th c pht hin trong phn. - Dc ng hc: Sau khi dc cht c hp thu th nng dc cht trong mu c duy tr trong sut khong thi gian dng thuc l 6gi. - Liu dng: Liu c th ti 50 mg/kg th trng/24 gi. Trng lng 88-110Ib (60-70kg) 132-154Ib (80-90kg) 176-198Ib (80-90kg) >220Ib( >100kg) - Ch phm: Procan SR 250MG: mu xanh l cy, hnh elip, bao phim, phng thch ko di. Liu lng 500mg/6gi 750mg/6gi 1g/6gi 1,25g/6gi

Procan SR 500MG : mu vng, hnh elip, bao phim, phng thch ko di.

Procan SR 750MG : cam, hnh elip, bao phim, phng thch ko di.

Procan SR 1000MG: mu , hnh elip, bao phim, phng thch ko di.

d. Copley - CopLey l vin nn, dng phng thch ko di. [33] Liu lng: 500 mg/8 gi. Liu c th ti 50 mg/kg th trng/24 gi, chia lm 4 - 6 gi/ln v vi vin chm chia lm 3 - 4 ln. Ch phm: COPLEY 188: Cha 500mg procainamide hydrochloride.

COPLEY 114: Cha 750mg procainamide hydrochloride.

COPLEY 115: Cha 1000mg procainamide hydrochloride.

6.2.1.3. Nhn xt i vi vin nn khng c tc dng ko di: 250 - 500 mg/3 - 4 gi, v vin chm: 500 mg/8 gi. Liu c th ti 50 mg/kg th trng/24 gi, chia lm 4 - 6 gi/ln v vi vin chm chia lm 3 - 4 ln. Nh vy khi dng thuc c tc dng ko di th s gim c s ln dng thuc, trnh qun thuc, b thuc, m bo s tun th ca ngi bnh theo ch liu ch nh, nng cao hiu qu iu tr. c bit bnh nhn b bnh tim mch trnh c nhng cn bc pht gy nguy him n tnh mng do nng thuc khng trong c th. 6.2.2. Quinidin 6.2.2.1. Ch phm quy c a. Tinh cht ly hoa - CTPT: C20H24N2O2 M = 324,43

- Quinidin l 1 alkaloid, cht rn kt tinh mau trng nhit phng. L ng phn D ca quinin (alcaloid ca cy Cinchona - Rubiaceae). Bin mau khi tip xuc khng khi, anh sang. D tan trong ethanol, tan c trong nc. [54] b. Dc ng hoc - Hp thu tt qua ng ung (>90%), sinh kha dung ng ung khoang 80%, 30 phut sau ung xut hin tac dung. Nng ti a trong huyt tng sau 1-3 gi. - Gn vao protein huyt tng khoang 80%. Thuc tp trung nhiu gan, thn, thng thn, tim va c vn. - Chuyn hoa gan thanh 2-hydroxy quinidin. T1/2 = 4-10 gi, keo dai ngi suy tim, gan, thn. - Thai tr qua nc tiu dang a chuyn hoa (khoang 95%). Kim hoa nc tiu lam giam thai tr thuc nn keo dai tac dung. [54] c. Chi inh - liu dung Chi inh - Tt nht trong rung nhi, cung ng nhi. - Nhip nhi nhanh. - Ri loan nhip khi xut hin tao nhip t phat. [54] Dang bao ch - Quinidin c nhiu dng mui khc nhau (sulfat, polygalacturonat v gluconat) v c nhiu dng liu khc nhau (vin nang, vin nn v dng tim). Co ch phm dang dn xut la dihydroquinidin hydroclorid, dihydroquinidin gluconat. - Dang vin: + Quinidin sulfat, dihydroquinidin hydroclorid vin nen 0,2 - 0,3g; vin nang 0,3g. + Quinidin galacturonat: vin nen 275mg. - Dang tim quinidin sulfat 0,2g/1mL, 0,5g/1mL

Liu dung Vin Quinidin sulfat, dihydroquinidin hydroclorid u tng ng 165mg quinidin base Ngay th nht: ung 1 vin 2 ln Ngay th hai: ung 1 vin 4 ln Ngay th ba: ung 1 vin 5 ln Co th dung tip tuc 7 ngay, mi ngay 5 vin hoc dung liu duy tri 1-2 vin/ngay/thang. [54] 6.2.2.2. Ch phm co dang TDKD Quinidex Extentabs Cng thc bao ch: Quinidin sulfate (tng ng 249 mg quinidin base) Ta dc: acacia, acetylat monoglycerid, calcium sulfate, sap carnauba, edible ink, FD&C Blue 2, gelatin, guar gum, magnesium oxide, magnesium stearate, polysorbates, shellac, sucrose, titanium dioxide, sap trng va mt s phm mau khac. Liu dung: 1 vin Quinidex (tng ng 249 mg quinidin base) mi 8-12h. [36]

Hinh anh 6.2.3. Disopyramid 6.2.3.1. Ch phm quy c a. Dc ng hoc

D hp thu qua ng ung, d dung nap. Sinh kha dung ng ung khoang 50%. Gn nhiu vao protein huyt tng. Thi gian ban thai khoang 6-8 gi. Thai tr qua thn. [54] b. Chi inh - liu dung Chi inh: Thay th quinidin, procainamid trong ri loan nhip tht khi 2 thuc o khng hiu qua hoc khng dung nap thuc. Ch phm va liu dung - Vin nang 0,10g-0,15g, ng 5mL cha 50mg. Ung: 1 vin/ln cach 6 gi. 6.2.3.2. Ch phm TDKD Norpace CR - Vin nang 100mg, 150mg, 300mg cha disopyranmide phosphate - Thnh phn ta dc: tinh bt ng, ethylcellulose, gelatin, sucrose talc, titan dioxit, D & C Yellow10, edible ink, FD& C Blue 1 - Nng thuc n nh n 12h sau i vi vin nang 300mg. - Liu dng: ngi ln : 600mg/ngy chia i liu (300mg /12h). i vi nhng bnh nhn c trng lng c th t hn 50kg liu lng khuyn co la 400mg/ngy chia i liu (200mg/12h). [29]

7. Thuc ha lipid mau 7.1. Niacin 7.1.1.1. Ch phm quy c

a. Tinh cht ly hoa - Tinh th hnh kim khng mu, khng mi, v chua. - Tan trong nc, ethanol, ethyl ether. Khng tan trong cc dung mi hu c khng phn cc. [22] b. Dc ng hoc Niacin hp thu qua ng ung, khuch tn vo cc m, chuyn ha gan v thi tr qua nc tiu. Thi gian bn thi t 20-45 pht. [22; 50] c. Chi inh - liu dung Cc liu quy c: 25mg, 50mg, 100mg, 250mg, 500mg Ch nh: Niacin dng cha bnh pellagra, ngoi ra cn c s dng gim cholesterol v triglyceride trong mu. C th, n lm gim cholesterol xu (LDL cholesterol) v lm tng cholesterol tt (HDL cholesterol). Niacin lm gim sn xut cc protein vn chuyn cholesterol v triglycerides trong mu. Liu dng: Ngi ln: 1,5-3 g/ngy chia liu, c th tng ln n 6 g/ngy nu cn. Niacin nn c bt u vi liu thp v tng chm hn vi tun vai tun sau. [23] [50] 7.1.1.2. Ch phm tac dung keo dai Liu ca ch phm ko di: 125 mg, 250 mg, 500 mg, 750 mg, 1000 mg. Mt s bit dc TDKD: [23] [24] [38] STT 1 2 3 4 Tn bit dc Niaspan ER Niacin SR Slo - niacin Niacor Thnh phn niacin niacin niacin niacin Hm lng 1000mg; 750mg; 500mg 125mg; 500mg 250mg; 500mg; 750mg 500mg Dng bo ch Vin nn Vin nang c cha cc ht gii phng ko di Vin nang Vin nn

5

Simcor

Kt hp ca niacin v simvastatin.

500/20mg; 500/40mg; 750/20mg; 1000/20mg

Liu ti a l 2 g mi ngy. Ty theo tnh trng bnh, v th trng bnh nhn c liu lng thuc thch hp cho tng i tng Mt vi hnh nh:

Niacin SR 125mg

Niaspan 500 mg

Niaspan 1000 mg

Niaspan 750 mg

slo niacin 250mg

slo niacin 500mg

Niacor 500mg - Phng php bo ch: vin nn niacin 375 mg tc dng ko di 12 gi c th bo ch bng phng php dp thng vi t dc to ct l gm xanthan hoc metholose. T l cc t dc trong vin, nht l t dc to ct c nh hng ln n s gii phng dc cht t vin. Metholose c kh nng kim sot gii phng dc cht tt hn gm xanthan. [49] 7.1.1.3. Nhn xet Ch phm Niacin tc dng ko di iu tr tng lipid mu gip gim s ln s dng thuc. Hn ch vic qun s dng thuc, nht l cc bnh nhn ln tui, cc bnh nhn b bnh mn tnh nh bnh tim mch. Dng ch phm ko di cng gip duy tr u n nng thuc trong mu, trnh tnh trng dao ng nng thuc trong mu qua gip gim cc tc dng ph. Liu iu tr ca cc ch phm bnh thng l 1,5 3g trong ngy, vy liu ti a trong 1ngy l 6g trong khi liu iu tr ca thuc tc dng ko di l 2g trong 1ngy. Ta nhn thy lng hot cht a vo c th khi s dng vin gii phng chm t hn nhng tc dng vn khng i. 7.2. Bezafibrate 7.2.1.1. Ch phm quy c a. Tinh cht ly hoa - Cng thc phn t: C19H 20ClNO 4

- Bezafibrate l bt kt tinh. Nhit nng chy: 649,68 K, nhit si: 1004,15 K - Bezafibrate ha tan trong cc dung mi hu c nh ethanol, DMSO, v dimethyl formamide (DMF). tan ca bezafibrate trong ethanol l khong 3 mg/ml v khong 30 mg/ml trong DMSO v DMF, tan trong nc: 0,5 mg/ml 25,0 oC - Khi lng phn t: 361.8194 vC [5] b. Dc ng hoc Bezafibrat c hp th ng tiu ha khi ung trong ba n, nhng s hp th s km khi i v b gim i rt nhiu nu ung sau khi nhn i qua m. Bezafibrat d dng b thy phn thnh cht chuyn ha c hot tnh, lin kt nhiu vi albumin huyt tng, do y cc thuc khng vitamin K ra khi v tr gn vi protein huyt tng ca chng. Nng nh huyt tng t c trong vng 2 n 4 gi sau khi ung thuc. Trn 95% thuc gn vi protein huyt tng, gn nh duy nht vi albumin. Th tch phn b: 0,2 lt/kg Thuc c phn b rng v tp trung gan, thn v rut 60% n 90% liu ung thi tr vo nc tiu v mt t vo phn, ch yu di dng lin hp glucuronic. Thi gian bn thi l 1-2 gi. [5] [45] c. Chi inh - liu dung Ch nh lm sng: L mt thuc h tr cho ch n ung v cc bin php iu tr bnh nhn tng cholesterol mu Loi IIa v IIb tng lipid mu hn hp, nhm iu chnh mc lipid v apoprotein (gim huyt thanh TG, LDL cholesterol, apolipoprotein B, tng cholesterol HDL v apolipoprotein A); iu tr bnh nhn c mc cht bo trung tnh cao n rt cao, phn loi Fredrickson loi IV v hyperlipidemias V, nhng ngi ang c nguy c cao ca di chng v bin chng t ri lon lipid mu ca h (vim ty). Bezafibrate khng c iu tr y mt s bnh nhn tng lipid mu gia nh kt hp vi loi IIb v loi IV hyperlipoproteinemia.

Liu s dng: 1vin /ln. 2-3 ln/ngy. [45] 7.2.1.2. Ch phm tac dung keo dai Bezalip 400 mg Sustained-Release Hm lng 400mg. Liu dng 1 vin/ngy. 7.2.1.3. Nhn xet Liu iu tr ca cc ch phm bnh thng l 200mg x 2- 3ln/ ngy, vy liu ti a trong 1ngy l 600mg trong khi liu iu tr ca thuc tc dng ko di l 400 mg trong 1ngy. Lng hot cht a vo c th khi s dng vin gii phng chm t hn nhng tc dng vn khng i.

TAI LIU THAM KHAO 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. Adalat LA 30 mg, www.drugs.com Adalat retard 20 mg, www.medicines.ie/ Adalat retard 20mg, http://www.thuocbietduoc.com.vn Betaloc Zok, www.astrazeneca.com Bezafibrate, www.caymanchem.com Cardizem CD Extended Release, www.accessdata.fda.gov Cordipatch, http://drugs-about.com/drugs-c/cordipatch.html Diafusor, http://www.orca-inst.com/diafusor.html iu tr mt s ri lon nhp tim thng gp (k 1) www.tailieu.vn Dilrene LP G 300 mg Glule libration prolonge Bote de 28, http://santeaz.aufeminin.com Diltahexal 90mg retard, http://duocphamvn.com Diltiazem, http://duocthu.com Diltiazem hydroclorid, http://www.thuocmoi.com.vn Glyceryltrinitrat, http://duocthu.com Half-Inderal LA www.astrazeneca.com Isosorbide dinitrate, Isosorbide mononitrate http://www.mims.com Lenitral, www.mims.com Lenitral capsule, www.mims.com.my/ Metoprolol, http://www.thuocbietduoc.com.vn Metoprolol succinat, http://www.drugbank.ca Monotrat, http://www.ykhoanet.com/duoc/duocpham/tracuu/DM002817.htm Niacin - Compound Summary, www.pubchem.ncbi.nlm.nih.gov Niacin (vitaminB3, acid nicotianic), www.medpill.info Niacin SR, www.drugs.com Nifedipin, http://duocthu.com Nitro-Bid, http://www.buy-cheap-pharma.com/Nitroglycerin_Ointment-p-166.html Nitroderm TTS, www.drugs.com/international/nitroderm-tts.html Nitroglycerin, http://vi.wikipedia.org Norpace CR, http://www.rxlist.com/norpace-drug.htm Pentaerythritol tetranitrate www.pubmed.com Procainamid, http://duocthu.com Procainamid hydrochlorid, www.elephantcare.org Procainamid hydrochlorid SR, www.drugs.com Procan-SR, www.rxlist.com Propranolol, http://www.thuocbietduoc.com.vn Quinidex, http://www.rxlist.com/quinidex-drug.htm Risordan, http://www.ykhoanet.com/duocpham/tracuu/DM001957.htm Simcor, www.cholesterol.emedtv.com Thuc chen beta adrenergic, www.benhhoc.com Thuc chng ri lon nhp, www.bacsivn.com Vastarel, www.tailieu.vn Vastarel MR, http://yduocngaynay.com

43. 44. 45. 46. 47. 48. 49. 50. 51.

52. 53. 54. 55.

(2002), Dc in Vit Nam, Nxb. Y hoc, III. (2009), Vidal Vit Nam. The comprehensive resource for physicians, www.rxmed.com Nguyn Huy Dung (2003), Tim mch hc - Bi ging h Ni khoa, Nxb. Y hoc. Rajeev Gupta, Jitendra P.S., Sawhney,Varun S. Narain Am (2005), J Cardiovasc Drugs 5 (5), 325-329. Trn Thi Thu Hng (2011), Dc lc hoc, Nxb. Phng ng, TP. H Chi Minh. Phm Th Minh Hu (2009), Nghin cu bo ch vin nn niacin tc dng ko di dng ct thn nc Tap chi dc hoc, (394). Niacin, www.medicinenet.com Genissel P, Chodjania Y, Demolis JL,et al (2004), Assessment of sustained release properties of a new oral formulation of trimetazidine in pigs and dogs and confirmation in healthy human volunteers, Eur J Drug Metab Pharmacokinet, 20 (1), 61-68. ao Vn Phan, Nguyn Trong Thng,Nguyn Trn Giang Hng (2005), Dc l hc lm sng, Nxb. Y Hoc, Ha Ni. Phm Thip,V Ngc Thu (2006), Thuc bit Dc v cch s dng, Nxb. Y hoc, Ha Ni. Mai Tt T,Vu Thi Trm (2007), Dc l hc, Nxb. Y hc, H Ni, 2. Mai Tt T,Vu Thi Trm (2007), Dc ly hoc, Nxb. Y hoc, Ha Ni, 1.